The purpose of this application is to evaluate the impacts of methamphetamine and a range of social, structural, and environmental factors on initiation into injection drug use, HIV risk behavior and sexually transmitted infection (STI) incidence among street-involved youth. Globally, it is estimated that there are as many as 100 million street-involved youth, and illicit drug use and related harms (e.g., infectious diseases) have consistently been shown to be elevated among this population. Thus, there is an urgent need for data to inform interventions aimed at addressing the health needs of this growing population. In particular, given the challenges preventing harms (e.g., HIV infection) that occur after youth begin drug injecting, data to inform strategies to prevent initiation into injection drug use are urgently needed. We propose to undertake this work in a western Canadian setting where the explosive growth in methamphetamine use has mirrored a steady growth in the use of this drug in the western United States. While these trends are a source of growing concern due to methamphetamine's relationship with rising HIV risk behavior among men who have sex with men and adult IDU, the epidemiology of methamphetamine use and its relationship to sexual and injection-related HIV risk behavior remain poorly defined. Vancouver, Canada, is ideally suited for the proposed study for several reasons. First, the city is presently experiencing an explosive rise in the use of methamphetamine among street-involved youth, and past experience demonstrates that drug market trends in Vancouver are often reflected in other western US cities, and the city is known to be a North American port of entry for several illicit drugs and precursor chemicals which subsequently flow into the US. Thus, this research will provide valuable data to inform US drug trends and interventions. Vancouver is also home to a large and visible street-youth problem and street-based illicit drug market, and the risk environment in which street youth become involved in illicit drugs has not been well described. Herein, we propose to create an open prospective cohort study of 500 street-involved youth aged 14 to 25 who will complete a standardized questionnaire and provide biological specimens on a semi-annual basis. Given the local drug use and risk environment characteristics, as well as the local laboratory capacity, our proposed research plan offers an ideal opportunity to examine the impact of evolving drug use patterns and a range of social, structural, and environmental factors on the rates of initiation into injection drug use, sexual risk behavior and STI incidence. This research also presents a unique opportunity to create a cohort of street-involved non-injecting youth which will enable comparisons with an ongoing study of adult injection drug users. Together, this research will address several questions central to the urgent challenges facing street-involved youth in North America as a result of the growth of methamphetamine use and illicit drug injecting, and will allow for the evaluation of a range of individual and contextual determinants of HIV risk behavior and STI incidence among this population. PUBLIC HEALTH RELEVANCE: While increasing methamphetamine use among youth is a source of growing concern due to methampheta- mine's relationship with rising HIV risk behavior among men who have sex with men and adult injection drug users, the epidemiology of methamphetamine use and its relationship to initiation of injection drug use, HIV risk behaviour, and sexually transmitted infection incidence among high-risk youth remains poorly defined. This research will fill this void by evaluating patterns of methamphetamine use and other illicit drug patterns, as well as the risk environment in which drugs are used, to describe their effects on initiation of injection drug use, sexual risk behavior, and incidence of sexually transmitted infections among a cohort of 500 street-involved youth.